College of Arts and Sciences, University of Maine at Augusta, Bangor, ME, United States.
Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME, United States.
Front Immunol. 2021 May 7;12:636623. doi: 10.3389/fimmu.2021.636623. eCollection 2021.
The inflammatory response to viral infection in humans is a dynamic process with complex cell interactions that are governed by the immune system and influenced by both host and viral factors. Due to this complexity, the relative contributions of the virus and host factors are best studied using animal models. In this review, we describe how the zebrafish () has been used as a powerful model to study host-virus interactions and inflammation by combining robust forward and reverse genetic tools with imaging of transparent embryos and larvae. The innate immune system has an essential role in the initial inflammatory response to viral infection. Focused studies of the innate immune response to viral infection are possible using the zebrafish model as there is a 4-6 week timeframe during development where they have a functional innate immune system dominated by neutrophils and macrophages. During this timeframe, zebrafish lack a functional adaptive immune system, so it is possible to study the innate immune response in isolation. Sequencing of the zebrafish genome has revealed significant genetic conservation with the human genome, and multiple studies have revealed both functional conservation of genes, including those critical to host cell infection and host cell inflammatory response. In addition to studying several fish viruses, zebrafish infection models have been developed for several human viruses, including influenza A, noroviruses, chikungunya, Zika, dengue, herpes simplex virus type 1, Sindbis, and hepatitis C virus. The development of these diverse viral infection models, coupled with the inherent strengths of the zebrafish model, particularly as it relates to our understanding of macrophage and neutrophil biology, offers opportunities for far more intensive studies aimed at understanding conserved host responses to viral infection. In this context, we review aspects relating to the evolution of innate immunity, including the evolution of viral pattern recognition receptors, interferons and interferon receptors, and non-coding RNAs.
人类对病毒感染的炎症反应是一个动态过程，具有复杂的细胞相互作用，受免疫系统调控，并受到宿主和病毒因素的影响。由于这种复杂性，最好使用动物模型来研究病毒和宿主因素的相对贡献。在这篇综述中，我们描述了如何通过结合强大的正向和反向遗传工具以及对透明胚胎和幼虫进行成像，利用斑马鱼（）作为一种强大的模型来研究宿主-病毒相互作用和炎症。固有免疫系统在对病毒感染的初始炎症反应中起着至关重要的作用。由于斑马鱼在发育过程中有一个 4-6 周的时间窗口，其固有免疫系统由中性粒细胞和巨噬细胞主导，具有功能性固有免疫系统，因此可以对病毒感染的固有免疫反应进行集中研究。在这段时间内，斑马鱼缺乏功能性适应性免疫系统，因此可以单独研究固有免疫反应。斑马鱼基因组的测序显示与人类基因组有显著的遗传保守性，多项研究表明，包括那些对宿主细胞感染和宿主细胞炎症反应至关重要的基因，其功能也具有保守性。除了研究几种鱼类病毒外，还开发了几种人类病毒的斑马鱼感染模型，包括甲型流感病毒、诺如病毒、基孔肯雅热、寨卡病毒、登革热、单纯疱疹病毒 1 型、辛德毕斯病毒和丙型肝炎病毒。这些多样化的病毒感染模型的发展，加上斑马鱼模型固有的优势，特别是与我们对巨噬细胞和中性粒细胞生物学的理解有关，为更深入地研究宿主对病毒感染的保守反应提供了机会。在这种情况下，我们回顾了与固有免疫进化相关的方面，包括病毒模式识别受体、干扰素和干扰素受体以及非编码 RNA 的进化。
